Identification of postsynaptic phosphatidylinositol-4,5-bisphosphate (PIP₂) roles for synaptic plasticity using...

Phosphatidylinositol-4,5-bisphosphate (PIP₂), one of the key phospholipids, directly interacts with several membrane and cytosolic proteins at neuronal plasma membranes, leading to changes in neuronal properties including the feature and surface expression of ionotropic receptors. Although PIP₂ is also concentrated at the dendritic spines, little is known about the direct physiological functions of PIP₂ at postsynaptic as opposed to presynaptic sites. Most previous studies used genetic and pharmacological methods to modulate enzymes that alter PIP₂ levels, making it difficult to delineate time- or region-specific roles of PIP₂. We used chemically-induced dimerization to translocate inositol polyphosphate 5-phosphatase (Inp54p) to plasma membranes in the presence of rapamycin. Upon redistribution of Inp54p, long-term depression (LTD) induced by low-frequency stimulation was blocked in the mouse hippocampal CA3-CA1 pathway, but the catalytically-dead mutant did not affect LTD induction. Collectively, PIP₂ is critically required for induction of LTD whereas translocation of Inp54p to plasma membranes has no effect on the intrinsic properties of the neurons, basal synaptic transmission, long-term potentiation or expression of LTD.